We have applied quantitative scanning transmission electron microscopy (STEM) and energy-filtered transmission electron microscopy (EFTEM) to elucidate the molecular organization of amyloid proteins involved in Azheimers Disease. Abnormal deposits of amyloid beta protein (Ab) in the brain of Alzheimer's patients occur as fibrils within the cerebral neuropil. To characterize the way in which these fibrils assemble under different pH conditions, we have performed scanning transmission electron microscopy (STEM) on synthetic full-length Ab peptides as well as various Ab peptides with truncated sequences. STEM analysis of unstained preparations provides a quantitative determination of the mass-per-length (MPL) and thus the numbers of beta-sheets within fibrils. We have also investigated the use of inelastic dark-field imaging in the energy-filtering transmission electron microscope (EFTEM) as an alternative approach to determining the MPL of amyloid fibrils. Images were collected with an incident electron energy of 300 keV, and energy losses in the range 15 to 35 eV, which corresponds to the broad plasmon resonance for protein. The inelastic EFTEM mass maps were found to be of comparable quality to the STEM mass maps in terms of the signal to noise ratio, but the EFTEM images could be acquired more rapidly. In general, MPL measurements reveal the existence of fundamental fibrillizing units, or "protofilaments," consisting of well-defined numbers of cross-beta sheets. Specifically, we have found twisted fibrils that contain three beta sheets, whose structure has been correlated with atomic-level information about the peptide backbone conformation by our collaborators in NIDDK using NMR spectroscopy. We are currently investigating the morphology and subunit organization in fibrils of mutant amyloid peptides, such as the arctic mutation. We have also characterized the ultrastructure of amyloid beta fibrils that were seeded from fibrils extracted from brain tissue of deceased Azheimers Disease patients. Because amyloid structures propagate themselves in seeded growth, as shown in our previous studies, the molecular structures of brain-seeded synthetic beta amyloid fibrils most likely reflect structures that are present in Azheimers Disease brain. Electron microscopy data complemented solid-state NMR spectroscopy data. The results demonstrate a new approach to detailed structural characterization of amyloid fibrils that develop in human tissue, and to investigations of possible correlations between fibril structure and the degree of cognitive impairment and neurodegeneration in Alzheimers Disease.